Researchers suggest that dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, may improve ventricular arrhythmia in pulmonary arterial hypertension (PAH), as published in Bioengineered.
“Dapagliflozin reversed the structural and electrical remodeling of ventricles by preventing the activated signal pathway of TLR4 [toll-like receptor 4]/NF-κB [nuclear factor kappa B], reducing the vulnerability of ventricular arrhythmia caused by PAH,” the authors explained.
The study was performed using a monocrotaline-induced PAH rat model. Rats were randomized into 4 groups: control (n=20), control+dapagliflozin (n=20), PAH (n=20), or PAH+dapagliflozin (n=20). Dapagliflozin was administered in drinking water at a concentration of 60 mg/L for 4 weeks.
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The main findings of the study were as follows:
- Dapagliflozin prevented the occurrence of right heart failure, ventricular hypertrophy and fibrosis, which were observed in the untreated PAH group. Hypertrophy and fibrosis are well-recognized hallmarks of pathological ventricular remodeling
- Dapagliflozin reduced the ratio and duration of ventricular arrhythmia. It decreased from 80% in the untreated PAH group to 30% in the dapagliflozin-treated group
- Dapagliflozin shortened the action potential duration (APD) measured at 20%, 50%, and 90% repolarization, and prolonged the effective refractory period (ERP). It also increased the expression of ion channel proteins, such as Cav1.2, Kv1.5, Kv2.1, Kv4.2, and Kv4.3, whose downregulation has been associated with prolonged APD and shorted ERP
- Dapaglifloz ininhibited the activation of the TLR4/NF-κB signaling pathway, which is known to be involved in the development of ventricular remodeling and heart failure
- PAH rats treated with dapagliflozin presented with lower body weight than untreated PAH rats, but with higher blood glucose and blood pressure
These results are in agreement with other studies that suggest that dapagliflozin attenuates heart failure and ventricular arrhythmia.
Qin T, Kong B, Dai C, et al. Protective effects of dapagliflozin on the vulnerability of ventricular arrhythmia in rats with pulmonary artery hypertension induced by monocrotaline. Bioengineered. 2022;13(2):2697-2709. doi:10.1080/21655979.2021.2017652